Stories about: genes

Getting a grip on genetic loops

Chromatin is housed inside the nucleus. A new discovery about its physical arrangement could pave the way for new therapeutics.
Artist’s rendering of chromatin, which is housed inside the nuclei of mammalian cells. A new discovery about its physical arrangement could pave the way for new therapeutics.

A new discovery about the spatial orientation and physical interactions of our genes provides a promising step forward in our ability to design custom antibodies. This, in turn, could revolutionize the fields of vaccine development and infection control.

“We are beginning to understand the full biological impact that the physical structure and movement of our genes play in regulating health and development,” says Frederick Alt, PhD, director of the Boston Children’s Hospital Program in Cellular and Molecular Medicine (PCMM) and the senior author of the new study, published in the latest issue of Cell.

Recent years of research by Alt and others in the field of molecular biology have revealed that it’s not just our genes themselves that determine health and disease states. It’s also the three-dimensional arrangement of our genes that plays a role in keeping genetic harmony. Failure of these structures may trigger genetic mutations or genome rearrangements leading to catastrophe.

The importance of genetic loops

Crammed inside the nucleus, chromatin, the chains of DNA and proteins that make up our chromosomes, is arranged in extensive loop arrangements. These loop configurations physically confine segments of genes that ought to work together in a close proximity to one another, increasingly their ability to work in tandem.

“All the genes contained inside one loop have a greater than random chance of coming together,” says Suvi Jain, PhD, a postdoctoral researcher in Alt’s lab and a co-first author on the study.

Meanwhile, genes that ought to stay apart remain blocked from reaching each other, held physically apart inside our chromosomes by the loop structures of our chromatin.

But while many chromatin loops are hardwired into certain formations throughout all our cells, it turns out that some types of cells, such as certain immune cells, are more prone to re-arrangement of these loops.

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Patients’ brain tissue unlocks the cellular hideout of Sturge-Weber’s gene mutation

A diagram of the skull and brain showing the leptomeninges, which is affected by Sturge-Weber syndrome
Sturge-Weber syndrome causes capillary malformations in the brain. They occur in the brain’s leptomeninges, which comprise the arachnoid mater and pia mater.

A person born with a port-wine birthmark on his or her face and eyelid(s) has an 8 to 15 percent chance of being diagnosed with Sturge-Weber syndrome. The rare disorder causes malformations in certain regions of the body’s capillaries (small blood vessels). Port-wine birthmarks appear on areas of the face affected by these capillary malformations.

Aside from the visible symptoms of Sturge-Weber, there are also some more subtle and worrisome ones. Sturge-Weber syndrome can be detected by magnetic resonance imaging (MRI). Such images can reveal a telltale series of malformed capillaries in regions of the brain. Brain capillary malformations can have potentially devastating neurological consequences, including epileptic seizures.

Frustratingly, since doctors first described Sturge-Weber syndrome over 100 years ago, the relationship between brain capillary malformations and seizures has remained somewhat unexplained. In 2013, a Johns Hopkins University team found a GNAQ R183Q gene mutation in about 90 percent of sampled Sturge-Weber patients. However, the mutation’s effect on particular cells and its relationship to seizures still remained unknown.

But recently, some new light has been shed on the mystery. At Boston Children’s Hospital, Sturge-Weber patients donated their brain tissue to research after it was removed during a drastic surgery to treat severe epilepsy. An analysis of their tissue, funded by Boston Children’s Translational Neuroscience Center (TNC), has revealed the cellular location of the Sturge-Weber mutation. The discovery brings new hope of finding ways to improve the lives of those with the disorder.

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Stem cell medicine gets a “roadmap” and a quality assurance tool

cell fate map Boston subway
Credit: Samantha Morris, PhD, Boston Children’s Hospital

If you’ve lost your way on the Boston subway, you need only consult a map to find the best route to your destination. Now stem cell engineers have a similar map to guide the making of cells and tissues for disease modeling, drug testing and regenerative medicine. It’s a computer algorithm known as CellNet.

As in this map on the cover of Cell, a cell has many possible destinations or “fates,” and can arrive at them through three main stem cell engineering methods:

reprogramming (dialing a specialized cell, such as a skin cell, back to a stem-like state with full tissue-making potential)
differentiation (pushing a stem cell to become a particular cell type, such as a blood cell)
direct conversion (changing one kind of specialized cell to another kind)

Freely available on the Internet, CellNet provides clues to which methods of cellular engineering are most effective—and acts as a much-needed quality control tool.

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Will the Supreme Court’s decision on “gene patents” stifle medical innovation?

(bobosh_t/Flickr)
The Supreme Court's ruling did not hand a clear victory to either party.(bobosh_t/Flickr)
Nicole D. Kling, PhD, is a patent specialist at Nixon Peabody LLP who focuses on patent prosecution in biotechnology, the life sciences and biomedical advances. David Resnick, JD, of Nixon Peabody contributed to this post. Opinions expressed in this article represent only those of the authors, not Nixon Peabody or its clients.

The recent ruling by the U.S. Supreme Court brought Association for Molecular Pathology v. Myriad Genetics back to the headlines, with interest being stoked by Angelina Jolie’s recent disclosure of her double mastectomy.

The lawsuit revolved around patents owned by Myriad related to its BRACAnalysis test, which assesses the likelihood that a person will develop certain cancers, including breast cancer, by searching the DNA for disease-causing sequences. The patents under focus in this lawsuit claim genetic sequences isolated from, or derived from, human DNA—molecules created by manipulating, changing or adding to the DNA.

Myriad argued that the molecules they claimed do not exist as such in human cells and are instead the result of human manipulation and innovation.

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Fetal DNA tests: Are we finally entering an era of eugenics?

Eugenics, 1919. (Photo: A.M. Kuchling/Flickr)

As an Ashkenazi Jew planning to have a baby, I sure as heck wanted carrier screening for Tay-Sachs disease. But that disease is incurable and lethal. What about diseases that don’t severely limit lifespan and aren’t that disabling? During my pregnancy, I went on to have amniocentesis, which included testing for Down syndrome and – because of my family history — for a few genes associated with autism and mental retardation. But even as I was tested, I had no idea what I’d do if results came back positive.

Sometime soon, almost every expectant family may be faced with such life-and-death decisions. New tests are arriving that can detect Down syndrome by analyzing fetal DNA in the mother’s blood during the first trimester of pregnancy.

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